Wire for medical use coated with polyether sulphone and a copolymer

ABSTRACT

The invention relates to a wire for medical use comprising a substrate provided with a first layer and a polymer layer applied thereto, whereby said first layer is polyether sulphone and said polymer layer is a hydrophilic copolymer built up of an N-vinyl lactam compound and an alkyl (meth)acrylate compound. The invention furthermore relates to a method for producing the same and to the copolymer to be used therefor.

The present invention relates to a wire for medical use comprising asubstrate provided with a first layer and a polymer layer appliedthereto. The present invention furthermore relates to a method forproducing such a wire.

A wire of this type for medical use is known from European PatentApplication 0 389 632. Said European patent application relates to amedical instrument having good sliding properties, such as an instrumentused for catheterisation, whereby the surface of a base material, whichis coated with a component A, is coated with component B. A polymerhaving at least one reactive functional group selected from the groupconsisting of alkali metal alcoholate groups, amino group, alkali metalamide groups, carboxylic acid group, sulphonic acid group, magnesiumhalogenide groups and fluorinated boron complex groups is used ascomponent A. A hydrophilic polymer having a reactive heterocyclic groupbeing reactive with the reactive functional groups in the component A isused as component B. Several plastics, metallic wires, stainless steel,ceramics and wood are named as the base material. Component A ispreferably applied to the base material by dipping or spincoating, usinga solution in which a specified amount of component A is dissolved,followed by drying. The proportion of component A in the solution mayrange from 0.01-50% by weight. Alcohols, halogenated hydrocarbons,ketones, amides and linear or cyclic hydrocarbons are named as solvents.The surface of the base material, which is coated with component A, isthen coated with component B dissolved in a solvent, using the samemethod as used for applying component A. After component B has beenapplied a reaction is effected between component A and component B byusing a heat treatment.

From European Patent Application 0 166 998 a medical instrument is knownwhich comprises a substrate containing a reactive functional group, atleast on its surface, which group is covalently bound to a water-solublepolymer or a derivate thereof, as a result of which a lubricating effectis obtained by contacting the treated surface with water. Examples ofthe reactive functional groups include a diazonium group, azide group,isocyanate group, acid chloride group, acid anhydride group, iminocarbonate group, amino group, carboxyl group, epoxy group, hydroxylgroup and aldehyde group. The water-soluble polymer is selected from thegroup consisting of a cellulosic polymer, a maleic acid anhydridepolymer, a polyacrylamide and a water-soluble nylon or a derivativethereof.

Further research has shown that a guide wire for medical use, inparticular for diagnostic purposes such as catheterisation, must have avery smooth outer surface. During the diagnostic examination the guidewire is introduced into for example the patient's vascular system, andthe smooth outer surface of the guide wire ensures that the tissue, inparticular the walls of the blood vessels, is not damaged. Since theouter surface is very smooth, the amount of friction is quite low, sothat no tissue is damaged. In addition to that the smooth outer surfacemust comprise a hydrophilic polymer, which makes the guide wire smoothafter being immersed in an aqueous solution or a saline solution priorto being introduced into the human body.

The wire according to the invention as referred to in the introductionis characterized in that said first layer is polyether sulphone and thatsaid polymer layer is a hydrophilic copolymer built up of an N-vinyllactam compound and an alkyl (meth)acrylate compound.

The term "N-vinyl lactam compound" used herein is understood to includeN-vinyl pyrrolidone, N-vinyl butyrolactam, N-vinyl caprolactam and thelike. Examples of alkyl(meth)acrylate compounds are methyl methacrylate,ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, isobutylmethacrylate, hexyl methacrylate, methyl acrylate, ethyl acrylate,propyl acrylate and hexyl acrylate. The substrate according to theinvention is preferably a metal wire.

The hydrophilic copolymer as used on the wire according to the presentinvention is preferably built up of 1-30% by weight of alkyl(meth)acrylate compound and 99-70% by weight of N-vinyl-lactam compound.If the amount of alkyl (meth)acrylate compound in the hydrophiliccopolymer is more than 30% by weight, said hydrophilic copolymer willexhibit insufficient lubricating or sliding action. If the amount ofalkyl (meth)acrylate is less than 1% by weight, the hydrophiliccopolymer obtained will be insufficiently strong, resulting in aninsufficient adherence to the first layer.

The hydrophilic copolymer is preferably built up of N-vinyl pyrrolidoneand n-butyl methacrylate, and it is preferred for said monomericstructural units to be randomly distributed over the hydrophiliccopolymer. A random copolymer provides an excellent bond between thehydrophilic copolymer and the first layer consisting of polyethersulphone.

The average molecular weight of the hydrophilic copolymer preferablyranges from 50,000-400,000. If the average molecular weight is more than400,000, the copolymer obtained will be insufficiently flexible and willexhibit a poor bond to the first layer.

The thickness of the polymer layer is preferably 3-8 μm. If thethickness is less than 3 μm, the sliding properties obtained will beinsufficient, which may lead to the tissue being damaged. If thethickness is more than 8 μm, a guide wire which cannot be readilyspiralled or coiled is obtained.

The present invention furthermore relates to a method for producing thewire. According to this method a metal wire is cleaned in (preferably) abath of phosphoric acid, then the cleaned wire is passed through a bathof polyether sulphone, the metal wire comprising a layer of polyethersulphone is dried and then passed through a solution in which thehydrophilic copolymer is dissolved, after which the metal wirecomprising a polymer layer and a first layer is dried and then wound ona coil.

It is preferred to dissolve the hydrophilic copolymer in N-methylpyrrolidone in an amount of 10% by weight. It is not possible todissolve the hydrophilic copolymer in an amount of more than 10% byweight in N-methyl pyrrolidone, this in connection with the solubilityof the hydrophilic copolymer in the solvent N-methyl pyrrolidone.

The present invention furthermore relates to a copolymer built up of aN-vinyl lactam compound and an alkyl (meth)acrylate compound obviouslyintended for coating objects to be used for medical applications. Suchobjects also include implantation materials which are permanentlypresent in the human body.

The present invention will be explained in more detail with reference tothe following example and the appended FIGS. 1 and 2.

FIG. 1 is a graphic representation of the relative force which isrequired for pulling a guide wire provided with a hydrophilic copolymerthrough a polyurethane catheter as a function of the layer thickness ofthe hydrophilic copolymer.

FIG. 2 is a graphic representation of the relative force which isrequired for pulling a guide wire provided with a hydrophilic copolymerthrough a polyurethane catheter as a function of the proportion N-vinylpyrrolidone:n-butyl methacrylate in the hydrophilic copolymer.

FIG. 3 shows a cross section of a coated wire, comprising a wire coatedwith a first layer and a second layer.

FIG. 4 shows a partial cross section of the coated wire spiralled arounda spool.

The term relative force is understood to mean the force which isrequired for pulling a guide wire, made from a material according to thepresent invention, through a polyurethane catheter in comparison withthe force which is required for pulling a guide wire provided with aPTFE-layer through the same catheter.

EXAMPLE

The starting materials N-vinyl pyrrolidone and n-butyl methacrylate arecharged to a reaction vessel in a mol ratio of 90:10. Then a radicalinitiator and a chain transfer agent are added, after which the reactionmixture is subjected to a heat treatment in several stages. After saidheat treatment in several stages for 14 hours the hydrophilic copolymeris obtained in the form of a white or transparent material.Spectroscopic experiments with an NMR-apparatus have shown that thecopolymer is essentially free from monomeric components. The averagemolecular weight is 78,000, measured according to gel permeationchromatography. Then the copolymer is formed into grains, pulverized anddissolved in an amount of N-methyl pyrrolidone with a proportion of 1:9(1 part by weight of copolymer:9 parts by weight of solvent).

A stainless steel metallic wire having a diameter of 0.2 mm is cleanedby passing said wire through a bath of phosphoric acid, after which thewire is rinsed in a hot water bath and dried by blowing of hot air. Thenthe cleaned wire is passed through a 25% by weight solution of polyethersulphone in N-methyl pyrrolidone, as a result of which a polyethersulphone layer having a thickness of about 1 μm is obtained. Afterevaporation of the solvent at an elevated temperature the coated metalwire is passed through a 10% by weight solution of the aforesaidhydrophilic copolymer in N-methyl pyrrolidone. The wire is passedthrough the solution 2-3 times, in order to obtain a thickness of about5 μm, whereby the wire is dried at an elevated temperature each time ithas been passed through said solution. Then the metal wire, which is nowprovided with a first layer and a polymer layer applied thereto, isdried at an elevated temperature and wound on a spool. It is to beunderstood that a guide wire for medical use is obtained by separatingsaid wire from the spool and making a spring coil from the wire.

FIG. 3 shows a cross section of a coated wire 4, comprising a wire 1coated with a first layer 2 and a second layer 3. FIG. 4 shows a partialcross section of the coated wire 4 spiralled around a spool 5.

A wire provided with layers obtained in this manner was spiralled toform a spring, and subsequently data as shown in the respective FIGS. 1and 2 were obtained while varying the layer thickness of the hydrophiliccopolymer and the percentage of N-vinyl pyrrolidone in the hydrophiliccopolymer consisting of the respective monomeric components N-vinylpyrrolidone and n-butyl methacrylate. FIG. 1 shows the force which isrequired for pulling such an guide wire coated with a hydrophiliccopolymer through a polyurethane catheter as a function of the layerthickness of the hydrophilic copolymer. The molecular proportion ofN-vinyl pyrrolidone n-butyl methacrylate in the hydrophilic copolymer is90:10. This force has been compared with the force which is required forpulling a similar guide wire coated with a PTFE-layer through the samecatheter. In FIG. 1 this is shown as a straight line with a relativeforce having a value 1. FIG. 1 clearly shows that it is preferred forthe layer thickness to be more than 3 μm. FIG. 2 corresponds with FIG.1, wherein FIG. 2 the relative force is shown as a function of theproportion of the monomeric structural units in the copolymer. The layerthickness of the hydrophilic copolymer is 5 μm. From FIG. 2 it isapparent that the percentage of N-vinyl pyrrolidone in the hydrophiliccopolymer, consisting of the respective monomeric structural unitsN-vinyl pyrrolidone and n-butyl methacrylate, is preferably more than70%, because in such an embodiment the relative force, compared with aguide wire provided with a PTFE-layer, is less than 1.

What is claimed is:
 1. A wire for medical use comprising a substrateprovided with a first layer and a polymer layer applied to the firstlayer, wherein said first layer comprises polyether sulphone and saidpolymer layer comprises a hydrophilic copolymer built up of an N-vinyllactam compound and an alkyl (meth)acrylate compound.
 2. A wireaccording to claim 1, wherein said hydrophilic copolymer is built up of1-30% by weight of the alkyl (meth)acrylate compound and 99-70% byweight of the N-vinyl lactam compound.
 3. A wire according to claim 1,wherein said hydrophilic copolymer is built up of N-vinyl pyrrolidoneand n-butyl methacrylate.
 4. A wire according to claim 3, wherein theN-vinyl pyrrolidone and the n-butyl methacrylate are randomlydistributed over said hydrophilic copolymer.
 5. A wire according toclaim 1, wherein an average molecular weight of said hydrophiliccopolymer ranges from 50,000-400,000.
 6. A wire according to claim 1,wherein said polymer layer has a thickness, and wherein the thickness ofsaid polymer layer is 3-8 μm.
 7. A wire according to claim 1, whereinthe substrate comprises a metal wire.
 8. A method for producing a wireaccording to claim 1, wherein said wire is cleaned, the cleaned wire ispassed through a bath of polyether sulphone, then dried and passedthrough a solution of said hydrophilic copolymer and, after drying,wound on a spool.
 9. The use of a wire according to claim 1 as a guidewire for medical use.
 10. A wire according to claim 1, wherein the wireis a guide wire that is spiralled to form a spring.
 11. A wire formedical use as claimed in claim 1, wherein said hydrophilic copolymer isbuilt up of 1-30% by weight of N-vinyl pyrrolidone and 99-70% by weightof n-butyl methacrylate.
 12. An object for medical use comprising asubstrate having a first layer on the substrate and a polymer layerapplied to the first layer, wherein said first layer comprises polyethersulphone and said polymer layer comprises a hydrophilic copolymer of anN-vinyl lactam compound and an alkyl (meth)acrylate compound.
 13. Anobject for medical use as claimed in claim 12, wherein said hydrophiliccopolymer is built up of 1-30% by weight of the alkyl (meth)acrylatecompound and 99-70% by weight of the N-vinyl lactam compound.
 14. Anobject for medical use as claimed in claim 12, wherein said hydrophiliccopolymer is built up of N-vinyl pyrrolidone and n-butyl methacrylate.15. An object for medical use as claimed in claim 14, wherein theN-vinyl pyrrolidone and the n-butyl methacrylate are randomlydistributed over said hydrophilic copolymer.
 16. An object for medicaluse as claimed in claim 12, wherein an average molecular weight of saidhydrophilic copolymer ranges from 50,000-400,000.
 17. An object formedical use as claimed in claim 12, wherein said polymer layer has athickness, and wherein the thickness of said polymer layer is 3-8 μm.18. An object for medical use as claimed in claim 12, wherein thesubstrate comprises a material for implantation into a human body. 19.An object for medical use as claimed in claim 12, wherein the substratecomprises a wire.
 20. A method for producing an object for medical useas claimed in claim 12, wherein the method comprises:passing the objectthrough a bath comprising polyether sulphone; then drying the object andpassing the object through a solution comprising the hydrophiliccopolymer of the N-vinyl lactam compound and the alkyl (meth)acrylatecompound.
 21. A method as claimed in claim 20, wherein the substratecomprises a wire.
 22. A method as claimed in claim 21, wherein the wireis a guide wire that is spiralled to form a spring.
 23. A method asclaimed in claim 20, wherein said hydrophilic copolymer is built up of1-30% by weight of the alkyl (meth)acrylate compound and 99-70% byweight of the N-vinyl lactam compound.
 24. A method as claimed in claim20, wherein said hydrophilic copolymer is built up of N-vinylpyrrolidone and n-butyl methacrylate.
 25. A method as claimed in claim20, wherein the solution further comprises a solvent, and wherein thesolvent is a solvent for the hydrophilic copolymer and for the polyethersulphone.
 26. A method for producing an object for medical use asclaimed in claim 12, wherein the method comprises:passing the objectthrough a bath, wherein the bath comprises polyether sulphone in asolvent; then drying the object and passing the object through asolution, wherein the solution comprises the hydrophilic copolymerdissolved in the solvent, and wherein hydrophilic copolymer is acopolymer of the N-vinyl lactam compound and the alkyl (meth)acrylatecompound.
 27. A method as claimed in claim 26, wherein the solventcomprises N-methyl pyrrolidone.
 28. A method as claimed in claim 26,wherein the substrate comprises a wire.
 29. A method as claimed in claim28, wherein the wire is a metal wire.
 30. A method as claimed in claim28, wherein the wire is a guide wire that is spiralled to form a spring.31. A method as claimed in claim 26, wherein said hydrophilic copolymeris built up of 1-30% by weight of the alkyl (meth)acrylate compound and99-70% by weight of the N-vinyl lactam compound.
 32. A method as claimedin claim 26, wherein said hydrophilic copolymer is built up of N-vinylpyrrolidone and n-butyl methacrylate.
 33. An object for medical use asclaimed in claim 12, wherein said hydrophilic copolymer is built up of1-30% by weight of N-vinyl pyrrolidone and 99-70% by weight of n-butylmethacrylate.
 34. An object for medical use as claimed in claim 12,wherein the N-vinyl lactam compound is selected from the groupconsisting of N-vinyl pyrrolidone, N-vinyl butyrolactam, and N-vinylcaprolactam; and wherein the alkyl (meth)acrylate compound is selectedfrom the group consisting of methyl methacrylate, ethyl methacrylate,propyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, hexylmethacrylate, methyl acrylate, ethyl acrylate, propyl acrylate, andhexyl acrylate.